Genetics | The Smithsonian Institution's Human Origins Program
When scientists say there is a % difference in the DNA between humans and chimps, what data are they using? Looking at the evolution of different genes. Analogously, the greater similarity between humans and chimps than between So despite analyses of anatomy, the evolutionary relationships among many. Arizona State University, Tempe; and àSchool of Human Evolution and Social Change, Arizona State University, Tempe between human and chimpanzee genomes typically show .. the Y-chromosome may involve the difference in mating.
An estimate of TCHLCA at 10 to 13 million years was proposed in and a range of 7 to 10 million years ago is assumed by White et al. In effect, there is now no a priori reason to presume that human-chimpanzee split times are especially recent, and the fossil evidence is now fully compatible with older chimpanzee—human divergence dates [7 to 10 Ma Different chromosomes appear to have split at different times, possibly over as much as a 4-million-year period, indicating a long and drawn out speciation process with large-scale hybridization events between the two emerging lineages as late as 6.
This conclusion was rejected as unwarranted by Wakeleywho suggested alternative explanations, including selection pressure on the X chromosome in the populations ancestral to the CHLCA.
Hominini The taxon "tribe Hominini" was proposed on basis of the idea that, regarding a trichotomythe least similar species should be separated from the other two.
Originally, this produced a separated genus Homowhich, predictably, was deemed "most different" from the other two genera, Pan and Gorilla. However, later discoveries and analyses revealed that Pan and Homo are closer genetically than are Pan and Gorilla; thus, Pan was referred to the tribe Hominini with Homo.
DNA shapes how an organism grows up and the physiology of its blood, bone, and brains.
DNA is thus especially important in the study of evolution. The amount of difference in DNA is a test of the difference between one species and another — and thus how closely or distantly related they are. While the genetic difference between individual humans today is minuscule — about 0. The bonobo Pan paniscuswhich is the close cousin of chimpanzees Pan troglodytesdiffers from humans to the same degree. The DNA difference with gorillas, another of the African apes, is about 1.
Most importantly, chimpanzees, bonobos, and humans all show this same amount of difference from gorillas. A difference of 3. How do the monkeys stack up? Geneticists have come up with a variety of ways of calculating the percentages, which give different impressions about how similar chimpanzees and humans are.
A comparison of the entire genome, however, indicates that segments of DNA have also been deleted, duplicated over and over, or inserted from one part of the genome into another.
Identification of these human-specific loci makes them candidates for further inquiry.
Comparing the human and chimpanzee genomes: Searching for needles in a haystack
It is possible that some of these elements inserted into functional genes or flanking regions became alternatively spliced introns or promotor regulators, or either deleted or shuffled genomic regions via Alu-Alu recombination.
Look for human-specific gene conversions Another potential source of differences arises from species-specific gene conversion events that become fixed. Gene conversion homogenizes coding or noncoding sequences between adjacent paralogous gene copies within a species. Conversion may also introduce harmful mutations from a pseudogenized gene copy into a functional copy, or conversely, restore function to a former pseudogene.
This resulted in a change in sialic acid-binding properties, as well as new expression in human brain microglia. The gene-converted Siglec can thus be considered the first example of a human-specific protein.
More such examples might be found by systematically screening genomic regions, wherein genes and paralogous pseudogenes are nearby one another. Look for changes in noncoding regions A majority of comparative genomic studies have focused on coding regions at the expense of examining regulatory sequences Carroll However, given the relatively few protein-sequence differences between human and chimpanzees, differential regulation of gene and protein expression is a likely mechanism for explaining human: Functional noncoding regions such as promoters, enhancers, flanking sequences, and introns can regulate the expression of genes Wray et al.
The wealth of new information being generated about noncoding RNA sequences also makes them an intriguing candidates for potential differences Eddy ; Dykxhoorn et al.
Previous Section Next Section Genomic approach 3: Looking for human-specific gene expression differences As mentioned above, species-specific changes in genomic sequence can be manifested in regulatory processes such as timing and location of expression of genes or of functional noncoding sequences, such as siRNAs.
However, it is difficult to predict changes in expression simply by comparing genomic sequences Carroll Differences in expression pattern between humans and chimpanzees are being investigated using microarray analyses, which allow for a rapid screen of multiple loci expressed in a single tissue at a given time point.
Several such analyses and reanalyses have been carried out Enard et al. While the rate of brain gene expression changes appears increased in the human lineage, gene expression in the brain is overall more conserved than in other tissues, perhaps because of functional constraints in this complex organ Enard et al.
However, there are several caveats. For example, microarrays based on human oligonucleotide sequences may not accurately detect levels of expression in nonhuman primates nor detect significant alternative splicing of mRNAs Modrek and Lee ; Hsieh et al. Additionally, mRNA levels are not always good predictors of the actual levels of the gene product found in a cell Gygi et al.
Comparing the human and chimpanzee genomes: Searching for needles in a haystack
Moreover, a recent study suggests that most expression differences have little or no significance, and are likely due to neutral evolution Khaitovich et al. Any differences found need to be confirmed by focused biochemical studies on the molecules in question. Previous Section Next Section Candidate gene approaches In parallel with the above genomic studies, it is important to continue the more traditional candidate gene approach—as the genomic approach can miss many biologically significant differences.
The candidate approach focuses on specific genes, based on some a priori knowledge about which loci or system s might be expected to show functionally significant differences between humans and chimpanzees. Candidate gene approach 1: Making choices on the basis of comparative phenomics Humans and chimpanzees differ in many morphological, cognitive, and physiological arenas. When attempting to identify the genetic mechanisms responsible, it is logical to focus on genes known or predicted to contribute in some way to the phenotypic differences, i.
This can, in turn, allow us to identify appropriate candidate loci underlying the traits. We can then test them for their contribution to uniquely human traits affecting organs such as the skin, brain, and female reproductive system Table 1. Additionally, many diseases and pathological conditions appear to be unique to humans, and genes involved in some of these disease pathways are known or can be predicted Table 2. It makes sense to focus first on phenotypes or diseases that appear most directly relevant to explaining the human condition.
For example, recent work has suggested that two genes involved in the regulation of brain size appear to have undergone human-specific adaptive evolution Evans et al. A single genetic change may have had an impact on multiple organs, and such a change may be easier to study in organs other than the brain.Bonobo Chimpanzees: More human-like than you think
For example, there are organs such as the skin and its derivatives e. Genetic differences found in such systems may then help predict which molecules, pathways, or mechanisms have also undergone the most drastic changes during the evolution of the human brain. Candidate gene approach 2: Identifying such defects in the human population, particularly in families, provides an approach for directly linking genotype to phenotype and for choosing genes for human and chimpanzee comparisons.
The medical community in particular should be educated and vigilant about such opportunities. A striking outcome of this type of approach is FOXP2, a transcription factor shown to be associated with an inherited human disorder of speech production Enard et al.
The next step is to look at the consequences of such abnormal genotypes in vitro and by developing transgenic mice that manifest symptoms of the condition. Indeed, mice with a disruption in a single copy of the murine Foxp2 gene manifest a modest developmental delay and a significant alteration in ultrasonic vocalizations that are normally elicited when pups are removed from their mothers Shu et al. Another intriguing finding is that some amino acid sequence variants that cause disease in humans turn out to be a reversion to the conserved ancestral state, still present in the normal chimpanzee The Chimpanzee Sequencing and Analysis Consortium This phenomenon has been explained as being due to a high rate of compensatory mutations at other sites in the same protein.